Abstract
The adhesion of monocytes to vascular endothelial cells constitutes a fundamental early process in atherogenesis. Fibroblast growth factor-18 (FGF-18), known to signal through the fibroblast growth factor receptor 1 (FGFR1), has emerging roles in maintaining vascular homeostasis, but its precise function in endothelial inflammation remains unclear. The protective role of recombinant human FGF-18 (rhFGF-18) against oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury and its mechanism were investigated. We found that ox-LDL downregulated phospho-FGFR1 in human aortic vascular endothelial cells (HAVECs) dose- and time-dependently. rhFGF-18 treatment markedly suppressed ox-LDL-induced upregulation of the scavenger receptor LOX-1 and key pro-inflammatory factors (TNF-α, MCP-1, COX-2, and PGE2). Subsequently, rhFGF-18 reduced the expression of adhesion molecules VCAM-1 and ICAM-1, thereby decreasing THP-1 monocyte adhesion to HAVECs. Mechanistic investigations revealed that rhFGF-18 inhibits ox-LDL-induced phosphorylation and nuclear translocation of the transcriptional regulator TRIM28. Importantly, TRIM28 overexpression reversed the anti-inflammatory and anti-adhesive benefits of rhFGF-18. Collectively, this study identifies the FGF-18/TRIM28 axis as a crucial mechanism alleviating endothelial inflammation and monocyte adhesion, highlighting its potential as a therapeutic target for atherosclerosis.
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